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PLACENTAL ENDOCRINE DISRUPTION INDUCED BY CADMIUM (Cd): REDUCED EXPRESSION OF P450 CHOLESTEROL SIDE-CHAIN CLEAVAGE (P450scc) TRANSCRIPTS IN CULTURED HUMAN TROPHOBLASTS.
Kawai, Motoyuki 1,5, Swan, Kenneth1, Green, Amy1,4, Edwards, Deborah1,4, Anderson, Mary2,4, Henson, Michael1,2,3,4, 1 5 4 2 3
ABSTRACT- Maternal exposure to Cd, an environmental toxicant and constituent of tobacco smoke, has been associated with low birth weight. Recently, we reported that Cd inhibits the secretion of progesterone and the expression of low-density lipoprotein receptor mRNA in cultured human placental trophoblasts. Proper regulation of placental progesterone production is essential for the maintenance of primate pregnancy. Therefore, in the present study, we expanded our investigation to determine if Cd similarly influences the expression of P450scc, a rate-limiting enzyme involved in progesterone biosynthesis. Human placentae were obtained after uncomplicated cesarean section at term. Cytotrophoblasts were purified via density gradient centrifugation and were incubated for up to 96 h in Dulbeccos Modified Eagle Medium + 10% fetal bovine serum, which contained 0, 5, 10 or 20 M CdCl2. P450scc mRNA transcript abundance was determined by quantitative-competitive RT-PCR. Cell protein concentrations were estimated by Bradford assay and lactate dehydrogenase (LDH) activity was assessed in culture medium as a marker of cell injury and death. Cells progressed to syncytiotrophoblastic maturity, regardless of treatment. P450scc mRNA was lower (n=4, P<0.03) in cells co-cultured with 10 M CdCl2 for 96 h than in untreated controls. No apparent differences (P>0.05) were observed in mRNA transcript levels for the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase, in trophoblasts treated with 0 and 20 M CdCl2. In addition, no differences were observed in cell protein or LDH activity among trophoblasts treated with 0, 5 or 10 M CdCl2 for 96 h. Collectively, these results suggest a potentially detrimental role for Cd, specific to placental progesterone biosynthesis. Further studies will be required to fully elucidate the effects of environmental Cd on the maintenance of human pregnancy.
KEY WORDS: cadmium, placenta, trophoblast, P450 side-chain cleavage enzyme
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